Cyclophosphamide, a widely used alkylating agent produces premature ovarian failure in an age and dose dependent fashion. Patients are being followed to characterize the site and mechanism of follicular and endocrine toxicity of cyclophosphamide. Endocrine and follicular toxicity varies with treatment schedule and age, younger women being more resistant than older women, and daily treatment more toxic than intermittent treatment schedules. Treatment of non-human primates at different phases of the ovarian cycle suggests that the sensitivity of the ovary to cyclophosphamide varies during the cycle.